Diseases Commons^™

Design And Testing Of Novel Anthrax Vaccines Utilizing A Tobacco Mosaic Virus Expression System, Ryan C. Mccomb

KGI Theses and Dissertations

Anthrax is a potentially fatal disease caused by the bacteria Bacillus anthracis. Infection and disease occur after spores gain entry into the body, germinate into vegetative bacteria, and produce toxin. Bacillus anthracis spores have been engineered as bioweapons and have been used repeatedly in warfare and terrorism to inflict casualties in military and civilian populations. Currently, only one vaccine has been approved for prevention of anthrax in the United States. This vaccine is an undefined product that is difficult to produce, requires a long vaccination schedule, and is reactogenic. Efforts to make an improved anthrax vaccine are being pursued. …

Restoring Digestive Health, Kristin M. Corbin, Dnp, Aprn, Fnp-C

Doctor of Nursing Practice (DNP) Translational and Clinical Research Projects

Purpose: The purpose of this translational research project was to outline the healthcare problems associated with Functional Gastrointestinal Disorders and to explore the effectiveness of a gastrointestinal protocol utilized at Atlanta Center for Holistic and Integrative Medicine. The goal of this protocol is to restore digestive health with probiotics, digestive enzymes, and glutamine.

Background: Functional Gastrointestinal Disorders affect one in every four adults in the United States. These disorders encompass a variety of symptoms including diarrhea, constipation, cramping, abdominal pain, flatulence, reflux, and bloating without an identified physiological cause. There is currently no cure for Functional Gastrointestinal Disorders and treatment …

Lavender Oil: The New Sleep Aid, Audrey Nichols

University Honors Program

The purpose of this research paper is to discuss and evaluate the benefits of lavender oil within the general population and hospitalized patients. Specifically, this paper will look at aromatherapy use with lavender oil within the hospitalized population and it’s ability to better sleep quality within these patients. Sleep is a major factor in the boies ability to heal, and the hope of this research is to determine whether lavender oil would be an effective option for patients struggling with sleep disturbances during their hospital stay. In order to evaluate the effectiveness of lavender oil, previously conducted research articles and …

Viability Of Developmental Stages Of Schistosoma Mansoni Quantified With Xcelligence Worm Real-Time Motility Assay (Xworm)., Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Jeff T. Irelan, Michael J. Smout

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with helminth parasites causes morbidity and mortality in billions of people and livestock worldwide. Where anthelmintic drugs are available, drug resistance is a major problem in livestock parasites, and a looming threat to public health. Monitoring the efficacy of these medicines and screening for new drugs has been hindered by the lack of objective, high-throughput approaches. Several cell monitoring technologies have been adapted for parasitic worms, including video-, fluorescence-, metabolism enzyme- and impedance-based tools that minimize the screening bottleneck. Using the xCELLigence impedance-based system we previously developed a motility-viability assay that is applicable for a range of helminth parasites. …

Mechanisms By Which Dietary Ellagic Acid Attenuates Obesity And Obesity-Mediated Metabolic Complications, Inhae Kang

College of Education and Human Sciences: Dissertations, Theses, and Student Research

Ellagic acid (EA) is a polyphenol found in various fruits and plants, such as berries, pomegranates, muscadine grapes, nuts and bark of oak tree. EA has been known to exhibit anti-inflammatory and anti-proliferative effects in various types of cancer. However, little is known about the effects of EA on obesity. Herein, 1) the lipid-lowering role of EA was identified in primary human adipose stem cells (hASCs) and human hepatoma Huh7 cells; 2) the molecular mechanisms by which EA attenuates adipogenesis by epigenetic modification were identified; 3) the effects of EA on high fat and high sucrose-mediated obesity was …

Development And Evaluation Of Amphotericin B Loaded Iron Oxide Nanoparticles For Targeted Drug Delivery To Systemic Fungal Infections, Pavan Balabathula

Theses and Dissertations (ETD)

A targeted nanotheronostic drug delivery system to diagnose and treat life threatening invasive fungal infections (IFIs) such as cryptococcal meningitis was designed, developed, characterized, and evaluated. To address the development processes, first, iron oxide nanoparticles (IONP) (34-40 nm) coated with bovine serum albumin (BSA), loaded and targeted with amphotericin B (AMB) (AMB-IONP) was formulated by applying a layer by layer approach. Several designs (A, B, C, D, & E) of AMB-IONP were developed and their physicochemical properties such as drug loading with HPLC method, particle size, poly dispersity index (PDI), and ζ-potential using dynamic light scattering (DLS) technique, morphology with …

Genetic Control Of Survival And Weight Loss During Pneumonic Burkholderia Pseudomallei (Bp) Infection, Felicia D. Emery

Theses and Dissertations (ETD)

Burkholderia pseudomallei (Bp) is a saprophytic, gram-negative aerobe and the causative agent of the disease melioidosis. Melioidosis is an infectious disease that occurs in humans and animals and is prevalent in Southeast Asia, northern Australia and other tropical areas. Transmission occurs through direct contact with the organism via ingestion, inhalation, or through open wounds and skin abrasions. Clinical presentation is extremely variable and can range from acute septicemia with bacterial dissemination to distant sites, to an isolated pulmonary infection. Treatment of melioidosis can be problematic because it is often difficult to diagnose and Bp is resistant to a diverse group …

Development Of Oral Vaccines Against Lyme Disease, Rita Raquel Dos Anjos De Carvalho E Melo

Theses and Dissertations (ETD)

Lyme Disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne disease in the United States and Europe. If left untreated, it can lead to permanent damage to the nervous and musculoskeletal systems. In some cases, patients that receive the recommended antibiotic therapy develop a debilitating health condition associated with substantial health care costs. Despite current preventive measures, the incidence and the geographic distribution of Lyme Disease continues to increase. Recent estimates from CDC suggest that the true number of cases of Lyme Disease in the US is approximately 300,000 per year. Yet, there is currently no vaccine …

Cyclin-Dependent Kinase Inhibitor P1446a Induces Apoptosis In A Jnk/P38 Mapk-Dependent Manner In Chronic Lymphocytic Leukemia B-Cells, Cody Paiva, J. Claire Godbersen, Ryan S. Soderquist, Taylor Rowland, Sumner Kilmarx

Dartmouth Scholarship

CDK (cyclin-dependent kinase) inhibitors have shown remarkable activity in CLL, where its efficacy has been linked to inhibition of the transcriptional CDKs (7 and 9) and deregulation of RNA polymerase and short-lived pro-survival proteins such as MCL1. Furthermore, ER (endoplasmic reticulum) stress has been implicated in CDK inhibition in CLL. Here we conducted a pre-clinical study of a novel orally active kinase inhibitor P1446A in CLL B-cells. P1446A inhibited CDKs at nanomolar concentrations and induced rapid apoptosis of CLL cells in vitro, irrespective of chromosomal abnormalities or IGHV mutational status. Apoptosis preceded inactivation of RNA polymerase, and was accompanied by …

Does The Expression Of Ki-67, P16 And Cox-2 At Initial Diagnosis Of Breast Atypia Or Usual Ductal Hyperplasia Predict A Second Clinically Significant Event?, Judy A. Tjoe, Philippe Gascard, Jianxin Zhao, Gary F. Neitzel, Maharaj Singh, Brittany Last, James Marx, Thea Tlsty, Sanjay Kansra

Journal of Patient-Centered Research and Reviews

Background: Women diagnosed with atypical ductal hyperplasia (ADH) or atypical lobular hyperplasia (ALH) have a fivefold increased risk of developing breast cancer. Because ADH/ALH can be precursors or predictive markers of a subsequent clinically significant event (SCSE), i.e. atypia, in situ or invasive carcinoma, the clinical outcome for these patients ranges anywhere from remission to invasive malignancy. Currently we cannot predict which atypical breast lesion is likely to be associated with future cancer, resulting in aggressive management and, possibly, overtreatment. Kerlikowske et al. reported that a combination of three biomarkers (cell cycle regulator p16INK4a, proliferation antigen Ki-67 and stress response …

In Vitro Growth Suppression Of Renal Carcinoma Cells By Curcumin, Santhi Konduri, Madhavi Latha Yadav Bangaru, Phu Thanh Do, Shenglin Chen, Jeffrey Woodliff, Sanjay Kansra

Journal of Patient-Centered Research and Reviews

Background: Malignant clear cell renal carcinoma (ccRCC) is an aggressive tumor that is highly resistant to chemotherapy and radiation. Current therapeutic approaches to management of ccRCC have not significantly improved patient survival, therefore novel therapies are needed. The von Hippel-Lindau tumor suppressor gene is frequently mutated in ccRCC resulting in unregulated transcriptional activity of hypoxia-inducible factors (HIF) 1α and 2α. HIF-mediated transcription leads to increased growth factor expression and growth factor receptor (GFR)-mediated signaling. NFκB and STAT3 are phosphorylated in response to GFR activation and modulate gene expression, which promotes cell growth and invasion. Activated NFκB and STAT3 expression is …

Feasibility Of Atrial Delivery And Tracking Of Stem Cells In A Porcine Model, Nina Garlie, Timothy Hacker, Eric G. Schmuck, Jill Koch, Jayant Khitha, Amish Raval, Indrajit Choudhuri

Journal of Patient-Centered Research and Reviews

Background: Many patients undergoing open heart surgery have sinus node dysfunction and atrial fibrillation, leading to adverse outcomes. Mesenchymal stem cells (MSC) delivered at the time of surgery may have a reparative effect on atrial tissue, thereby improving sinus node function and reducing or preventing atrial fibrillation. Stem cell delivery to the atrium is entirely unstudied. This is a significant gap in medical research, as atrial disease contributes significantly to health care costs.

Purpose: The purpose of this pilot study is to establish a technique to deliver MSC to the atria through an open-chest model, to assess the safety of …

Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi

School of Medicine Faculty Publications

The HIV-1 transactivator protein Tat is implicated in the neuronal damage that contributes to neurocognitive impairment affecting people living with HIV/AIDS. Aberrant splicing of TAU exon 10 results in tauopathies characterized by alterations in the proportion of TAU isoforms containing three (3R) or four (4R) microtubule-binding repeats. The splicing factor SC35/SRSF2 binds to nuclear RNA and facilitates the incorporation of exon 10 in the TAU molecule. Here, we utilized clinical samples, an animal model, and neuronal cell cultures and found that Tat promotes TAU 3R up-regulation through increased levels of phosphorylated SC35, which is retained in nuclear speckles. This mechanism …

Carcinogenic Liver Fluke Secretes Extracellular Vesicles That Promote Cholangiocytes To Adopt A Tumorigenic Phenotype, Sujittra Chaidayet, Javier Sotillo, Michael Smout, Cinzia Cantacessi, Malcolm Jones, Paul J. Brindley, Jeffrey M. Bethony, +9 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background. Throughout Asia there is an unprecedented link between cholangiocarcinoma and infection with the liver fluke Opisthorchis viverrini. Multiple processes including chronic inflammation and secretion of parasite proteins into the biliary epithelium drive infection towards cancer. Until now, the mechanism and effects of parasite protein entry into cholangiocytes was unknown.

Methods. Various microscopy techniques were used to identify O. viverrini extracellular vesicles (EVs) and their internalization by human cholangiocytes. Using mass spectrometry we characterised the EV proteome and associated changes in cholangiocytes after EV uptake, and detected EV proteins in bile of infected hamsters and humans. Cholangiocyte proliferation and …

Tuberculosis And Cardiovascular Disease: Linking The Epidemics, Moises A. Huaman, David Henson, Eduardo Ticona, Timothy R. Sterling, Beth A. Garvy

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The burden of tuberculosis and cardiovascular disease (CVD) is enormous worldwide. CVD rates are rapidly increasing in low- and middle-income countries. Public health programs have been challenged with the overlapping tuberculosis and CVD epidemics. Monocyte/macrophages, lymphocytes and cytokines involved in cellular mediated immune responses against Mycobacterium tuberculosis are also main drivers of atherogenesis, suggesting a potential pathogenic role of tuberculosis in CVD via mechanisms that have been described for other pathogens that establish chronic infection and latency. Studies have shown a pro-atherogenic effect of antibody-mediated responses against mycobacterial heat shock protein-65 through cross reaction with self-antigens in human vessels. Furthermore, …

Cross-Sectional Survey Of Relevant Literatures As To The Current Proposed Disease Mechanisms And Treatments Of Amyotrophic Lateral Sclerosis (Als), Zachary Sanford

Marshall Journal of Medicine

Amyotrophic Lateral Sclerosis (ALS), more commonly referred to as Lou Gehrig’s disease, is a progressively degenerative neuromuscular disorder affecting both the upper and lower motor neurons and preferentially affecting males in their forties to seventies. Although the pathology of ALS has been clearly elucidated elsewhere, the precise mechanisms by which the disease progresses and the means by which it is acquired are still poorly understood areas of medicine. Current genomic and proteomic studies in human and animal models have yielded exciting and promising new findings that may help elucidate this pathology. It is the purpose of this review article to …

Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter

Biology Student Publications

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in …

Advances In The Diagnosis Of Human Opisthorchiasis: Development Of Opisthorchis Viverrini Antigen Detection In Urine, Chanika Worasith, Christine Kamamia, Anna Yakovleva, Kunyarat Duenngai, Chompunoot Wangboon, Jeffrey M. Bethony, +8 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Many strategies to control opisthorchiasis have been employed in Thailand, but not in the other neighbouring countries. Specific control methods include mass drug administration (MDA) and health education to reduce raw fish consumption. These control efforts have greatly shifted the epidemiology of Opisthorchis viverrini (OV) infection over the last decade from presenting as densely concentrated "heavy" infections in single villages to widespread "light" OV infections distributed over wide geographical areas. Currently, the "gold standard" detection method for OV infection is formalin ethyl-acetate concentration technique (FECT), which has limited diagnostic sensitivity and diagnostic specificity for light OV infections, with OV …

We Are… Bridging Medicine And Science, Vol. 1, Issue 4, Fall 2015, Marshall University Biomedical Sciences

We Are... Bridging Medicine Science

No abstract provided.

Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing And Potentially Promotes Neoplasia., Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Paul J. Brindley, +11 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated …

Initial Validation Of A Novel Method Of Presurgical Language Localization Through Functional Connectivity (Fcmri), Stephanie M. Noble, Dustin Scheinost, Susan Y. Bookheimer, Patricia Walshaw, R Todd Constable, Christopher F. Benjamin

Yale Day of Data

OBJECTIVE: Neurosurgery is potentially curative in chronic epilepsy but can only be offered to patients if the surgical risk to language is known. Clinical functional magnetic resonance imaging (fMRI) is an ideal, noninvasive method for localizing language cortex yet remains to be validated for this purpose. We have recently presented a novel method for localizing language cortex. Here we present a preliminary evaluation of this method’s validity. We hypothesized language regions identified using this novel method would demonstrate stronger functional connectivity than randomly generated set of proximal networks. METHOD: fMRI data were collected from sixteen temporal lobe patients …

New Paradigms In The Treatment Of Acute Complicated And Uncomplicated Type B Aortic Dissection, Eric S. Weiss

Journal of Patient-Centered Research and Reviews

The treatment of acute type B aortic dissection is a rapidly evolving field, due in a large part to the advent of thoracic endovascular aortic repair (TEVAR). This review will summarize the current literature on the management of both complicated and uncomplicated type B dissections, with special attention paid to emerging evidence supporting earlier aggressive treatment.

Subclavian Vein Stenosis/Occlusion Following Transvenous Cardiac Pacemaker And Defibrillator Implantation: Incidence, Pathophysiology And Current Management, Brian O'Leary, Suhail Allaqaband

Journal of Patient-Centered Research and Reviews

Subclavian vein stenosis is a common, but usually asymptomatic, complication following cardiac device placement. In addition to reviewing the literature on incidence, pathogenesis and management options for this important clinical problem, we describe two cases of symptomatic subclavian vein occlusion following pacemaker/defibrillator placement and successful treatment with venoplasty and stenting.

Vascular Medicine: A ‘Primary’ Specialty, Mark W. Mewissen

Journal of Patient-Centered Research and Reviews

N/A

The Right Tool For The Job: Detection Of Soil-Transmitted Helminths In Areas Co-Endemic For Other Helminths, Maria V. Periago, Renata C. Diniz, Simone A. Pinto, Anna Yakovleva, Rodrigo Correa-Oliveira, David J. Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Due to the recent increased use of the McMaster (MM) fecal egg counting method for assessing benzimidazole drug efficacy for treating soil-transmitted helminth (STH) infections, the aim of the current study was to determine the operational value of including the MM method alongside the Kato-Katz (KK) fecal thick smear to increase the diagnostic sensitivity when STHs are co-endemic with trematode helminths (e.g., Schistosoma mansoni).

Methods

A cross-sectional study was conducted in school-aged children aged 4-18 years in the northeastern region of the State of Minas Gerais (Brazil), where Necator americanus, Ascaris lumbricoides, Trichuris trichiura, and S …

Adverse Effects Of Asparaginase In Pediatric Patients With Acute Lymphoblastic Leukemia, Chengcheng Liu

Theses and Dissertations (ETD)

Acute lymphoblastic leukemia (ALL) is the most common type of childhood cancer. Asparaginase is a critical treatment component for ALL. However, its use is complicated by adverse effects, such as hypersensitivity, osteonecrosis and pancreatitis.

Hypersensitivity to asparaginase typically requires discontinuation of current formulation and substitution with other formulations, but the differential diagnosis can be challenging, and the diagnostic utility of antibody tests is unclear. We comprehensively analyzed anti-Elspar (native E.coli asparaginase) IgG antibodies in 410 pediatric patients treated on an asparaginaseintensive front-line clinical trial. Of 169 patients (41.2%) who exhibited clinical allergy, 147 (87.0%) were positive for anti-Elspar antibody. Of …

Ankyrin-B And Mtor Complex 1 In The Regulation Of Electrical Activities In The Heart, Henry C. Wu, Henry C. Wu

Dissertations and Theses (Open Access)

The mammalian target of rapamycin complex 1 (mTORC1) activity is paramount in the regulation of electrical activities in the brain and the heart. In the brain, the tumor suppressor gene TSC2 encodes the protein product tuberin that interacts with hamartin to form a heterodimer Tuberous Sclerosis Complex (TSC) that regulates mTORC1. When TSC2 is disrupted, mTORC1 activity becomes dysregulated resulting in abnormal electrical activities in the brain manifesting in the form of epileptic seizures. In the heart, mTORC1 activity is triggered by a sustained increase in hemodynamic pressure causing the heart to electrically remodel. A likely candidate serving as the …

Amikacin Concentrations Predictive Of Ototoxicity In Multidrug-Resistant Tuberculosis Patients, Chawangwa Modongo, Jotam G. Pasipanodya, Nicola M. Zetola, Scott M. Williams

Dartmouth Scholarship

Aminoglycosides, such as amikacin, are used to treat multidrug-resistant tuberculosis. However, ototoxicity is a common problem and is monitored using peak and trough amikacin concentrations based on World Health Organization recommendations. Our objective was to identify clinical factors predictive of ototoxicity using an agnostic machine learning method. We used classification and regression tree (CART) analyses to identify clinical factors, including amikacin concentration t

hresholds that pre- dicted audiometry-confirmed ototoxicity among 28 multidrug-resistant pulmonary tuberculosis patients in Botswana. Amika- cin concentrations were measured for all patients. The quantitative relationship between predictive factors and the probability of ototoxicity were then identified using …

Myasthenia Gravis, Abbe R. Feaver

Nursing Student Class Projects (Formerly MSN)

Myasthenia gravis (MG) is a chronic autoimmune neuromuscular disease characterized by ocular, bulbar, facial, and skeletal muscle weakness due to a defect in the transmission of nerve to muscle impulses at the neuromuscular junction (Mestecky, 2013, p. 110). Approximately 14-20 in 100,000 people are diagnosed with myasthenia gravis in the United States (Leis, Moore, Kofler, Beric, De Visser, 2014, p. 112). Typically, diagnosis occurs in middle-aged adults with women generally acquiring the disease at a younger age than men (Mestecky, 2013, p. 110). MG has the potential to greatly affect the quality of life of a patient. Although the disease …

Neurocysticercosis, Abigail Hill

Nursing Student Class Projects (Formerly MSN)

Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system in humans and is the most serious clinical manifestation of cysticercosis. NCC is caused by the ingestion of the larval form of the pork tapeworm Taenia solium. NCC is endemic in low income developing countries where pigs are commonly raised, including the countries of Central America, South America, and parts of Africa and Asia. (Naddaf, Seeger, & Stafstrom, 2014). The parasite Taenia solium encysts in the brain and can express a broad range of symptoms including seizures, headache, hydrocephalus, encephalitis, stroke and mental health and …